Lopinavir and Curcumin Directly Alters BAX/BCL2 and VEGF165b mRNA Levels to Suppress Human Squamous Cervical Carcinoma Cell Growth

Abstract

directly alters BAX/BCL2 and VEGF165b mRNA levels to suppress human squamous cervical carcinoma cell growth. Int. J. Morphol., 37(2):584-591, 2019. SUMMARY: Following the success of the highly active antiretroviral therapy, the potential of multidrug combination regimen for the management of cancer is intensely researched. The anticancer effects of curcumin on some human cell lines have been documented. Lopinavir is a FDA approved protease inhibitor with known apoptotic activities. Dysregulated apoptosis is important for the initiation of cancer while angiogenesis is required for cancer growth and development, this study therefore investigated the effects of the combination of lopinavir and curcumin on cell viability, apoptosis and the mRNA expression levels of key apoptotic and angiogenic genes; BAX, BCL2 and VEGF165b in two human cervical cell lines; human squamous cell carcinoma cells -uterine cervix (HCS-2) and transformed normal human cervical cells (NCE16IIA). The two human cervical cell lines were treated with physiologically relevant concentrations of the agents for 120 h following which BAX, BCL2 and VEGF165b mRNA expression were determined by Real Time qPCR. The Acridine Orange staining for the morphological evaluation of apoptotic cells was also performed. The combination of lopinavir and curcumin up-regulated pro-apoptotic BAX and antiangiogenic VEGF165b but down-regulated the mRNA levels of anti-apoptotic BCL2 mRNA in the human squamous cell carcinoma (HCS-2) cells only. The fold changes were statistically significant. Micrographs from Acridine Orange staining showed characteristic evidence of apoptosis in the human squamous cell carcinoma (HCS-2) cells only. The findings reported here suggest that the combination of curcumin and the FDA approved drug-lopinavir modulate the apoptotic and angiogenic pathway towards the inhibition of cervical cancer.

Curcumin: Modern Applications for a Versatile Additive

“…Due to the multitude of properties manifested by curcumin analogs, the diversity of applications of the natural compound will be further developed (Figure 2) as many as the issues related to the extraction, solubility, and stability of the parent compound will be solved. Due to its antioxidant and anti-inflammatory properties, modern applications of curcumin in the medical field targeting the treatment of neurodegenerative diseases [173][174][175][176] and cancer [177][178][179][180][181][182][183][184] will be further developed. Furthermore, studies have shown that, as a result of the metabolism process, curcumin can undergo two types of transformation.…”

“…In vivo studies have shown the hepato-protective and nephrological effect of curcumin administered before and during chemotherapy [178]. The second approach is the use of curcumin as an adjuvant with the effect of the chemosensitization of cancer cells resistant to chemotherapeutic agents, through mechanisms of inhibition of the expression of anti-apoptotic proteins or intracellular transcription factors [181]. Thus, the results of studies performed on patients with colorectal cancer refractory to standard chemotherapy established a daily oral dose of 3.6 g curcumin without adverse effects.…”

Caracterización Del Aceite Esencial De Clinopodium Revolutum Y Estudio Computacional De Sus Compuestos Bioactivos Contra El Cáncer

“…Sin embargo los reguladores apoptóticos que se encuentran en la familia BCL-2, son las responsables de modular el umbral de respuesta a una amplia variedad de estímulos apoptóticos implicados en varios tipos de carcinomas humanos 22,23 . En cambio el factor de crecimiento endotelial vascular VEGF y sus receptores VEGFR son indispensables en el proceso de regulación de la vascularización y angiogénesis 24,25 . La unión VEGF/VEGFR-2 activa las vías de señalización en la angiogénesis, siendo el VEGFR-2 el principal receptor de VEGF 26 .VEGFR-2 es el receptor de tirosina quinasa transmembrana que se correlaciona con la proliferación, división, motilidad, adhesión y angiogénesis celular, cuyo bloqueo inhibe la proliferación de células cancerosas 27 .…”