Dr. Bhol is currently working as a post doctoral fellow in the Department of Pharmacology, National University of Singapore. He has awarded his Ph.D. degree on the topic entitled "Unravelling the molecular connection between PAX9 and autophagy to regulate oral carcinogenesis" from the Department of Life Science, National Institute of Technology Rourkela, India. Prior to it he has done MTech in Agricultural Engineering from IIT Kharagpur and MSc in Life Science from NIT Rourkela.
RESEARCH INTERESTS
Cancer Biology
41
Scopus Publications
1952
Scholar Citations
21
Scholar h-index
27
Scholar i10-index
Scopus Publications
Pyrazoline–Imidazopyridine Hybrids as Beclin-1 Mimetics Driving Dual Apoptotic and Autophagy in Breast Cancer Rashmi Shivakumar, Narasimha M. Beeraka, Riyaz Ali M. Osmani, Bhoomika B. Ravi, Monisha H. S. Yadhav, et al. Chemical Biology and Drug Design, 2026 Breast cancer is a profound cause of mortality among women globally. Similar to BH3 mimetics, targeting the antiapoptotic Bcl‐xL:Beclin1 protein complex is crucial to inducing apoptosis and autophagy, thereby suppressing tumor progression in breast cancer cells. This study aims to synthesize and evaluate a series of imidazopyridine‐tethered pyrazoline drug prejudice‐scaffold derivatives (5a‐5l) as Beclin‐1 mimetics that induce apoptosis and autophagy and mainly for their potential anticancer activity, focusing on the most potent compound 5c. The primary goal is to assess its ability of compound 5c to inhibit Bcl‐xL:Beclin‐1 interaction, thereby inducing a protective autophagic response subsequently to assess apoptosis to suppress breast cancer cell proliferation. Molecular docking studies were conducted to evaluate the binding affinity of compound 5c with Bcl‐xL, and the interactions were visualized through a three‐dimensional interaction map, highlighting key stabilizing interactions. Cytotoxic effects of compound 5c on MCF‐7 breast cancer cells were assessed using alamarblue assay. To investigate the antiproliferative potential, colony formation, and wound healing assays were performed at varying concentrations. Apoptotic induction was analyzed through Western blotting for key proteins (BAX, Bcl‐xL, Bcl‐2), caspase‐3/7 activation, and AnnexinV/PI assay using flow cytometry. Additionally, autophagy was examined by monitoring LC3B‐I to LC3B‐II conversion, Beclin‐1 upregulation, and lysosomal activity using LysoTrackerRed staining. The involvement of compound 5c in autophagic flux was further confirmed by quantifying LC3‐II accumulation in the presence of an autophagy inhibitor chloroquine (CQ), and then the effect of 5c‐induced cell viability and apoptosis were evaluated and caspase‐3/7 activity, respectively, during autophagy inhibition condition in MCF‐7 cell line. A strong binding interaction of compound 5c with the hydrophobic groove of Bcl‐xL demonstrated its potential as an effective Bcl‐xL inhibitor. Compound 5c significantly reduced MCF‐7 cell viability in a dose‐dependent manner (IC50: 9.7 μM). The inhibitory effect of compound 5c on cancer cell proliferation and migration was observed. Treatment with compound 5c induced dose‐dependent apoptosis in MCF‐7 cells, as confirmed by Annexin V/PI using flow cytometric analysis after 72 h of exposure. A significant decrease in viable cells accompanied by an increase in apoptotic cell populations was observed with increasing concentrations of 5c. Upregulated BAX expression and downregulation in Bcl‐xL and Bcl‐2 expression levels indicated apoptosis induction. Caspase‐3/7 activation further confirmed apoptotic cell death. Autophagy assessment revealed enhanced LC3B‐II accumulation, Beclin‐1 upregulation, and reduced p62 levels, suggesting modulation of autophagy. CQ treatment further increased LC3‐II levels, indicating compound 5c‐mediated autophagic flux induction and a significant reduction in cell viability and increased caspase 3/7 activity, confirming modultion of autophagy‐dependent apoptosis by 5c. Similar to BH3 mimetic, compound 5c emerges as a promising small‐molecule inhibitor targeting the Bcl‐xL:Beclin‐1 complex, which effectively induces apoptosis by modulating protective autophagy in breast cancer cells. Its dual mechanism of action highlights its potential as a novel therapeutic candidate for breast cancer treatment.
1,2,3-Triazole Tethered Spiro[Indoline-Oxirane] Derivatives Induce Anticancer Effects in Human Hepatoma Cells Shashikala Mariswamy Rajesh, Prasanna Doddakunche Shivaramu, Chandra Sekhar Bhol, Toreshettahally R. Swaroop, Habbanakuppe D. Preetham, et al. Chemical Biology and Drug Design, 2025 Epoxides are well‐known compounds as anticancer agents. In this article, we present the synthesis of novel 3′‐phenyl‐1‐((1‐aryl‐1H‐1,2,3‐triazol‐5‐yl)methyl)spiro[indoline‐3,2′‐oxiran]‐2‐one derivatives by the regioselective reaction of sulfur ylides with 1,2,3‐triazole‐tethered isatins and their anticancer effects on hepatocellular carcinoma (HCC) cells HepG2 and HCCLM3. The cell viability assays indicated that RR‐01 and RR‐07 had emerged as the most potent cytotoxic agents on the tested cell lines. Colony formation and migration assay results confirmed the anticancer effects of these compounds by inhibiting the formation of colonies and migration. Further, nuclear fragmentation staining assay showed that the compounds induce apoptosis. Acridine orange staining assays showed that our lead candidates (RR‐01 and RR‐07) induced autophagy in liver cancer cells.
Discovery of Piperazin-2-yl-pyrimidines as Anticancer Agents via Targeting JNK Signaling Pathway in Human MCF-7 Breast Carcinoma Rashmi Shivakumar, Gautam Sethi, Kurnegala Manikanta, Zhang Xi, Akshay Ravish, et al. Chemistryselect, 2024 Breast cancer (BC) is the second leading cause of cancer‐related mortality in women, and targeting biological pathways such as the JNK pathway has proven to be a viable therapeutic target for BC therapy. Here, we synthesized piperazin‐2‐yl‐pyrimidines and evaluated them for anticancer activity against MCF‐7 cells. In addition, antioxidant, reactive oxygen species (ROS) inhibition, caspase activity, and toxicity in platelets were studied in the presence and absence of active compound IA‐6 or IA‐7. Our detailed experimental analysis found that the compound IA‐7 showed anticancer activity by either activating p‐JNK or by inducing radical species in cancer and thrombosis model. Evident to in vitro analysis, the structure based molecular interaction studies of binding of IA‐7 to JNK3S exhibited a significant binding energy of −7.56 kcal/mol which was found to be a better binder when compared to previously reported JNK inducer (PC‐12). Overall, we herein report the analytically pure IA‐7 as lead structure that could be used as a template to develop target based anticancer agents where JNK modulation is predominant.
Inflammasomes in cancer: Effect of epigenetic and autophagic modulations Soumya Ranjan Mishra, Kewal Kumar Mahapatra, Bishnu Prasad Behera, Chandra Sekhar Bhol, Prakash Priyadarshi Praharaj, et al. Seminars in Cancer Biology, 2022 Tumour-promoting inflammation is a critical hallmark in cancer development, and inflammasomes are well-known regulators of inflammatory processes within the tumour microenvironment. Different inflammasome components along with the adaptor, apoptosis-associated speck-like protein containing caspase activation and recruitment domain (ASC), and the effector, caspase-1, have a significant influence on tumorigenesis but in a tissue-specific and stage-dependent manner. The downstream products of inflammasome activation, that is the proinflammatory cytokines such as IL-1β and IL-18, regulate tissue homeostasis and induce antitumour immune responses, but in contrast, they can also favour cancer growth and proliferation by directing various oncogenic signalling pathways in cancer cells. Moreover, different epigenetic mechanisms, including DNA methylation, histone modification and noncoding RNAs, control inflammasomes and their components by regulating gene expression during cancer progression. Furthermore, autophagy, a master controller of cellular homeostasis, targets inflammasome-induced carcinogenesis by maintaining cellular homeostasis and removing potential cancer risk factors that promote inflammasome activation in support of tumorigenesis. Here, in this review, we summarize the effect of inflammasome activation in cancers and discuss the role of epigenetic and autophagic regulatory mechanisms in controlling inflammasomes. A proper understanding of the interactions among these key processes will be useful for developing novel therapeutic regimens for targeting inflammasomes in cancer.
Pyrazoline–Imidazopyridine Hybrids as Beclin‐1 Mimetics Driving Dual Apoptotic and Autophagy in Breast Cancer R Shivakumar, NM Beeraka, RAM Osmani, BB Ravi, MHS Yadhav, ... Chemical biology & drug design 107 (4), e70287 , 2026 2026
Synthesis and anti-proliferative studies of 2-acyl-4-(het) arylthiazoles on human hepatoma cells RN Suresh, PD Shivaramu, TR Swaroop, A Chinnathambi, SA Alharbi, ... Results in Chemistry, 102599 , 2025 2025
Harnessing Antineoplastic Properties of Artesunate for Prostate Cancer Therapy CS Bhol, MK Shanmugam, G Chew, GSR Eva, SK Bhutia, G Sethi Cancer Research 85 (15_Supplement), P47-P47 , 2025 2025
Autophagy paradox: Genetic and epigenetic control of autophagy in cancer progression CS Bhol, PK Senapati, RK Kar, G Chew, KK Mahapatra, EHC Lee, ... Cancer letters, 217909 , 2025 2025 Citations: 14
1, 2, 3‐Triazole Tethered Spiro [Indoline‐Oxirane] Derivatives Induce Anticancer Effects in Human Hepatoma Cells SM Rajesh, P Doddakunche Shivaramu, CS Bhol, TR Swaroop, ... Chemical Biology & Drug Design 105 (4), e70091 , 2025 2025 Citations: 1
Molecular regulation of mitophagy signaling in tumor microenvironment and its targeting for cancer therapy BP Behera, SR Mishra, S Patra, KK Mahapatra, CS Bhol, DP Panigrahi, ... Cytokine & growth factor reviews , 2025 2025 Citations: 18
Discovery of Piperazin‐2‐yl‐pyrimidines as Anticancer Agents via Targeting JNK Signaling Pathway in Human MCF‐7 Breast Carcinoma R Shivakumar, G Sethi, K Manikanta, Z Xi, A Ravish, PM Uppar, ... ChemistrySelect 9 (27), e202400307 , 2024 2024 Citations: 2
PAX9 activates cell death via autophagic degradation of EGFR in oral squamous cell carcinoma CS Bhol, G Sethi, SK Bhutia Cancer Research 84 (8_Supplement), P50-P50 , 2024 2024 Citations: 1
Synthesis of novel triazoles as anticancer agents targeting pJNK in human breast cancer cells TP Siddappa, CS Bhol, A Ravish, Z Xi, BC Narasimhachar, AM Kumar, ... New Journal of Chemistry 48 (26), 11662-11673 , 2024 2024 Citations: 3
Atg1/ULK1 complex in autophagy process and regulation CS Bhol, SK Bhutia Autophagy Process. Mech, 35 , 2023 2023 Citations: 2
PAX9 reactivation by inhibiting DNA methyltransferase triggers antitumor effect in oral squamous cell carcinoma CS Bhol, SR Mishra, S Patil, SK Sahu, R Kirtana, S Manna, ... Biochimica Et Biophysica Acta (BBA)-Molecular Basis of Disease 1868 (9), 166428 , 2022 2022 Citations: 31
Inflammasomes in cancer: Effect of epigenetic and autophagic modulations SR Mishra, KK Mahapatra, BP Behera, CS Bhol, PP Praharaj, ... Seminars in Cancer Biology 83, 399-412 , 2022 2022 Citations: 28
Autophagy-modulating phytochemicals in cancer therapeutics: Current evidences and future perspectives S Patra, SR Mishra, BP Behera, KK Mahapatra, DP Panigrahi, CS Bhol, ... Seminars in cancer biology 80, 205-217 , 2022 2022 Citations: 141
Unravelling the Molecular Connection Between Pax9 and Autophagy To Regulate Oral Carcinogenesis CS Bhol 2022
Metabostemness in cancer: linking metaboloepigenetics and mitophagy in remodeling cancer stem cells PP Naik, S Panigrahi, R Parida, PP Praharaj, CS Bhol, S Patil, ... Stem Cell Reviews and Reports 18 (1), 198-213 , 2022 2022 Citations: 17
Dspe-peg-coated uniform nitrogen-doped carbon capsules for nir-mediated synergistic chemophototherapy of skin cancer S Panda, CS Bhol, SK Bhutia, S Mohapatra ACS Applied Bio Materials 4 (9), 7059-7069 , 2021 2021 Citations: 6
The clinical significance and correlative signaling pathways of paired box gene 9 in development and carcinogenesis CS Bhol, S Patil, BB Sahu, SK Patra, SK Bhutia Biochimica et Biophysica Acta (BBA)-Reviews on Cancer 1876 (1), 188561 , 2021 2021 Citations: 21
Mitochondrial dysfunction as a driver of NLRP3 inflammasome activation and its modulation through mitophagy for potential therapeutics SR Mishra, KK Mahapatra, BP Behera, S Patra, CS Bhol, DP Panigrahi, ... The international journal of biochemistry & cell biology 136, 106013 , 2021 2021 Citations: 193
Intricate role of mitochondrial calcium signalling in mitochondrial quality control for regulation of cancer cell fate S Patra, KK Mahapatra, PP Praharaj, DP Panigrahi, CS Bhol, SR Mishra, ... Mitochondrion 57, 230-240 , 2021 2021 Citations: 20
Mitochondrial rewiring through mitophagy and mitochondrial biogenesis in cancer stem cells: A potential target for anti-CSC cancer therapy PP Praharaj, DP Panigrahi, CS Bhol, S Patra, SR Mishra, KK Mahapatra, ... Cancer letters 498, 217-228 , 2021 2021 Citations: 78
MOST CITED SCHOLAR PUBLICATIONS
The emerging, multifaceted role of mitophagy in cancer and cancer therapeutics DP Panigrahi, PP Praharaj, CS Bhol, KK Mahapatra, S Patra, BP Behera, ... Seminars in cancer biology 66, 45-58 , 2020 2020 Citations: 350
Mitochondrial dysfunction as a driver of NLRP3 inflammasome activation and its modulation through mitophagy for potential therapeutics SR Mishra, KK Mahapatra, BP Behera, S Patra, CS Bhol, DP Panigrahi, ... The international journal of biochemistry & cell biology 136, 106013 , 2021 2021 Citations: 193
Plant lectins in cancer therapeutics: Targeting apoptosis and autophagy-dependent cell death SK Bhutia, PK Panda, N Sinha, PP Praharaj, CS Bhol, DP Panigrahi, ... Pharmacological research 144, 8-18 , 2019 2019 Citations: 165
Autophagy-modulating phytochemicals in cancer therapeutics: Current evidences and future perspectives S Patra, SR Mishra, BP Behera, KK Mahapatra, DP Panigrahi, CS Bhol, ... Seminars in cancer biology 80, 205-217 , 2022 2022 Citations: 141
Intricate role of mitochondrial lipid in mitophagy and mitochondrial apoptosis: its implication in cancer therapeutics PP Praharaj, PP Naik, DP Panigrahi, CS Bhol, KK Mahapatra, S Patra, ... Cellular and Molecular Life Sciences 76 (9), 1641-1652 , 2019 2019 Citations: 111
Antitumor effect of soybean lectin mediated through reactive oxygen species-dependent pathway PK Panda, S Mukhopadhyay, B Behera, CS Bhol, S Dey, DN Das, ... Life sciences 111 (1-2), 27-35 , 2014 2014 Citations: 97
N-doped carbon quantum dot (NCQD)-Deposited carbon capsules for synergistic fluorescence imaging and photothermal therapy of oral cancer RK Das, S Panda, CS Bhol, SK Bhutia, S Mohapatra Langmuir 35 (47), 15320-15329 , 2019 2019 Citations: 84
Mitochondrial rewiring through mitophagy and mitochondrial biogenesis in cancer stem cells: A potential target for anti-CSC cancer therapy PP Praharaj, DP Panigrahi, CS Bhol, S Patra, SR Mishra, KK Mahapatra, ... Cancer letters 498, 217-228 , 2021 2021 Citations: 78
Epigenetic modifications of autophagy in cancer and cancer therapeutics CS Bhol, DP Panigrahi, PP Praharaj, KK Mahapatra, S Patra, SR Mishra, ... Seminars in cancer biology 66, 22-33 , 2020 2020 Citations: 75
Terminalia bellirica extract induces anticancer activity through modulation of apoptosis and autophagy in oral squamous cell carcinoma S Patra, PK Panda, PP Naik, DP Panigrahi, PP Praharaj, CS Bhol, ... Food and Chemical Toxicology 136, 111073 , 2020 2020 Citations: 73
Dysregulation of histone deacetylases in carcinogenesis and tumor progression: a possible link to apoptosis and autophagy S Patra, DP Panigrahi, PP Praharaj, CS Bhol, KK Mahapatra, SR Mishra, ... Cellular and molecular life sciences: CMLS 76 (17), 3263 , 2019 2019 Citations: 63
Rapid assessment of black tea quality using diffuse reflectance spectroscopy N Panigrahi, CS Bhol, BS Das Journal of Food Engineering 190, 101-108 , 2016 2016 Citations: 54
Secretory clusterin promotes oral cancer cell survival via inhibiting apoptosis by activation of autophagy in AMPK/mTOR/ULK1 dependent pathway PP Naik, S Mukhopadhyay, PP Praharaj, CS Bhol, DP Panigrahi, ... Life Sciences 264, 118722 , 2021 2021 Citations: 52
Bioactive compounds from marine invertebrates as potent anticancer drugs: the possible pharmacophores modulating cell death pathways S Patra, PP Praharaj, DP Panigrahi, B Panda, CS Bhol, KK Mahapatra, ... Molecular biology reports 47 (9), 7209-7228 , 2020 2020 Citations: 46
Molecular interplay of autophagy and endocytosis in human health and diseases KK Mahapatra, DP Panigrahi, PP Praharaj, CS Bhol, S Patra, SR Mishra, ... Biological Reviews 94 (4), 1576-1590 , 2019 2019 Citations: 45
Monitoring and measuring mammalian autophagy SK Bhutia, PP Praharaj, CS Bhol, DP Panigrahi, KK Mahapatra, S Patra, ... Autophagy in Differentiation and Tissue Maintenance: Methods and Protocols … , 2018 2018 Citations: 39
Gamma irradiation promotes chemo-sensitization potential of gallic acid through attenuation of autophagic flux to trigger apoptosis in an NRF2 inactivation signalling pathway S Patra, CS Bhol, DP Panigrahi, PP Praharaj, B Pradhan, M Jena, ... Free Radical Biology and Medicine 160, 111-124 , 2020 2020 Citations: 38
PAX9 reactivation by inhibiting DNA methyltransferase triggers antitumor effect in oral squamous cell carcinoma CS Bhol, SR Mishra, S Patil, SK Sahu, R Kirtana, S Manna, ... Biochimica Et Biophysica Acta (BBA)-Molecular Basis of Disease 1868 (9), 166428 , 2022 2022 Citations: 31
Inflammasomes in cancer: Effect of epigenetic and autophagic modulations SR Mishra, KK Mahapatra, BP Behera, CS Bhol, PP Praharaj, ... Seminars in Cancer Biology 83, 399-412 , 2022 2022 Citations: 28
PEG–PEI-modified gated N-doped mesoporous carbon nanospheres for pH/NIR light-triggered drug release and cancer phototherapy S Panda, CS Bhol, SK Bhutia, S Mohapatra Journal of Materials Chemistry B 9 (17), 3666-3676 , 2021 2021 Citations: 23