RESUMEN
The current study explored HPV prevalence and age variation in cervical samples of different cytological categories and HPV types from women seeking gynecological care in Tripura, northeast India. Pap smears, cervical tissues, and HPV/DNA specimens were collected from gynecological outpatient departments (OPD) or in-house patients and were screened for HPV16, HPV18, and other HPV types by PCR. Finally, logistic regression was performed to find the association between epidemiologic factors and HPV infection in women of different cytological grades. About 90% of HPV-screened women were found to be HPV positive. HPV16 was most common in HPV-positive women (53.27%), followed by HPV16/18 co-infection (26.17%). HPV16 or HPV18 was most frequent (86.45%) compared to others (13.55%). Among the confirmed cytological tests 68.83% showed normal cytology and 37.17% showed atypical abrasions. Among the abnormal cytology participants, 94.37% were HPV-positive, and 42.25% had cervical cancer. The prevalence of HPV increased with cytological abnormalities (p < 0.01). Abnormal cytological lesions increased with age (p trend = 0.017). Among all epidemiologic factors studied, parity was strongly associated with overall HPV infection, regardless of cytological status. Observed very high frequency of HPV infection in the current study, warrants further investigations.
RESUMEN
The anti-apoptotic proteins, Bcl-2 and Survivin, are consistently overexpressed in numerous human malignancies, notably in colorectal cancer. 2,4-Di-tert-butylphenol (2,4-DTBP) is a naturally occurring phenolic compound known for its diverse biological activities, including anti-cancer properties. The mechanism behind 2,4-DTBP-induced inhibition of cell proliferation and apoptosis in human colorectal cancer cells, specifically regarding Bcl-2 and Survivin, remains to be elucidated. In this study, we employed both in silico and in vitro methodologies to underpin this interaction at the molecular level. Molecular docking demonstrated a substantial binding affinity of 2,4-DTBP towards Bcl-2 (ΔG = -9.8 kcal/mol) and Survivin (ΔG = -5.6 kcal/mol), suggesting a potential inhibitory effect. Further, molecular dynamic simulations complemented by MM-GBSA calculations confirmed the significant binding of 2,4-DTBP with Bcl-2 (dGbind = -54.85 ± 6.79 kcal/mol) and Survivin (dGbind = -32.36 ± 1.29 kcal/mol). In vitro assays using HCT116 colorectal cancer cells revealed that 2,4-DTBP inhibited proliferation and promoted apoptosis in both a dose- and time-dependent manner. Fluorescence imaging and scanning electron microscopy illustrated the classical features associated with apoptosis upon 2,4-DTBP exposure. Cell cycle analysis through flow cytometry highlighted a G1 phase arrest and apoptosis assay demonstrated increased apoptotic cell population. Notably, western blotting results indicated a decreased expression of Bcl-2 and Survivin post-treatment. Considering the cytoprotective roles of Bcl-2 and Survivin through the inhibition of mitochondrial dysfunction, our findings of disrupted mitochondrial bioenergetics, characterized by reduced ATP production and oxygen consumption, further accentuate the functional impairment of these proteins. Overall, the integration of in silico and in vitro data suggests that 2,4-DTBP holds promise as a therapeutic agent targeting Bcl-2 and Survivin in colorectal cancer.
