Capsaicin synergizes with camptothecin to induce increased apoptosis in human small cell lung cancers via the calpain pathway

Abstract

Small cell lung cancer (SCLC) is characterized by excellent initial response to chemotherapy and radiation therapy with a majority of the patients showing tumor shrinkage and even remission. However, the challenge with SCLC therapy is that patients inevitably relapse and subsequently do not respond to the first line treatment. Recent clinical studies have investigated the possibility of camptothecin-based combination therapy as first line treatment for SCLC patients. Conventionally, camptothecin is used for recurrent SCLC and has poor survival outcomes. Therefore, drugs which can improve the therapeutic index of camptothecin should be valuable for SCLC therapy. Extensive evidence shows that nutritional compounds like capsaicin (the spicy compound of chili peppers) can improve the anti-cancer activity of chemotherapeutic drugs in both cell lines and animal models. Statistical analysis shows that capsaicin synergizes with camptothecin to enhance apoptosis of human SCLC cells. The synergistic activity of camptothecin and capsaicin is observed in both classical and variant SCLC cell lines and, in vivo, in human SCLC tumors xenotransplanted on chicken chorioallantoic membrane (CAM) models. The synergistic activity of capsaicin and camptothecin are mediated by elevation of intracellular calcium and the calpain pathway. Our data fosters hope for novel nutrition based combination therapies in SCLC.

Killing Two Angry Birds with One Stone: Autophagy Activation by Inhibiting Calpains in Neurodegenerative Diseases and Beyond

“…High calpain-2 expression was associated with the adverse clinical outcome of basal-like and triple-negative invasive breast cancer [31]. However, the proapoptotic or antineoplastic activity of capsaicin was found to be based on increased Ca 2+ levels and, thereby, calpain-1 and calpain-2 activation, in models of human small cell lung cancer [32, 33].…”

La combinación de docetaxel y capsaicina inhibe sinérgicamente el crecimiento de células de cáncer de próstata

“…Los datos recientes indican que la CAP presenta sinergismo con diversos fármacos convencionales como la camptotecina [8], la pirarubicina [19], la brasinina [10] y el resveratrol en varias líneas celulares tumorales [20]. Sin embargo, los mecanismos moleculares implicados en este efecto sinérgico siguen siendo en gran parte desconocidos.…”

“…Además, los datos recientes indican que la CAP sensibiliza las células a los agentes quimioterapéuticos. Por ejemplo, la combinación de CAP y camptotecina aumenta la apoptosis en cáncer de pulmón de células pequeñas [8]. En el colangiocarcinoma, la CAP aumenta la sensibilidad al 5-fluorouracilo y la mezcla de ambos compuestos inhibe el crecimiento del tumor con mayor eficacia que el 5-fluorouracilo [9].…”

Development of Fangjiomics for Systems Elucidation of Synergistic Mechanism Underlying Combination Therapy

“…Nevertheless, it's still a challenge to reveal the synergistic mechanism of combination therapy. Recently, the strategy used in prior studies was to analyze the effect of two drugs on a certain signaling receptor [ 14 ], enzyme [ 15 ], nucleotide [ 16 ] or process [ 17 ]. For example, synergistic reexpression of tumor suppressor gene, secreted frizzled-related protein 1 (sFRP1), was observed in combinatorial drug-treated groups of histone deacetylase (HDAC) inhibitor romidepsin and methyltransferase inhibitor [ 18 ].…”