Camptothecin, triptolide, and apoptosis inducer kit have differential effects on mitochondria in colorectal carcinoma cells

Abstract

Mitochondrial fission and fusion are required for cell survival, and several studies have shown an imbalance between fission and fusion in cancer. High levels of mitochondrial fusion are observed in drug‐resistant tumor cells, whereas mitochondrial fission may be important in sensitizing tumor cells to chemotherapy drugs. Based on current knowledge, we hypothesized that different chemotherapeutics might differentially affect mitochondrial dynamics and energy production. Thus, we selected chemotherapeutics with different mechanisms of action (camptothecin, triptolide and apoptosis inducer kit) and investigated their effect on mitochondria in colorectal carcinoma cells. We report that these chemotherapeutics decreased the activity of complex I and reduced the mitochondrial membrane potential, and also decreased the size of mitochondria in the colorectal carcinoma cell lines DLD1 and HCT‐116. Treatment with camptothecin, triptolide and/or apoptosis inducer kit results in differential effects of fission on apoptosis in these cells. Our results suggest that fission is an important process in apoptosis induced by chemotherapeutics.

Highly Sensitive Cyanine Dyes for Rapid Sensing of NAD(P)H in Mitochondria and First-Instar Larvae of Drosophila melanogaster

“…Camptothecin treatment of A549 cells causes DNA damage, activating DNA repair mechanisms. – This activation could result in an increased demand for NAD + since the enzyme poly­(ADP-ribose) polymerase (PARP), involved in DNA repair, consumes it. As a result, NADH and NADPH levels increase, impacting cellular processes, energy production, and ultimately contributing to antitumor effects and apoptosis …”

“…As a result, NADH and NADPH levels increase, impacting cellular processes, energy production, and ultimately contributing to antitumor effects and apoptosis. 62 Vancomycin functions as an antibiotic by binding to the terminal D-Ala-D-Ala residues, disrupting the synthesis of the bacterial cell wall. 63−65 However, it also has nonantibiotic effects, such as inhibiting the mitochondrial complex I enzyme that exerts a critical role in energy production and cellular respiration.…”

Mitochondrial fusion–fission dynamics and its involvement in colorectal cancer

“…In addition to the aforementioned small molecules of natural origin, the chemotherapeutic drugs triptolide and camptothecin, myoferlin inhibitor YQ456, and apoptosis inducer kit (AIK) stimulate DRP1 S616 phosphorylation and DRP1 S637 dephosphorylation. This dual action results in sustained mitochondrial fission, ultimately leading to cell death [ 73 , 74 ] (Fig. 2B ).…”

The therapeutic potential of natural products for treating pancreatic cancer

“…Accumulating evidences revealed that triptolide has a strong antitumor effect in a broad range of cancers, including non-small cell lung cancer (Zhou et al, 2022c), colorectal cancer (Liskova et al, 2022;Song et al, 2022), hepatocellular carcinoma (Li et al, 2022b), acute myeloid leukemia (Chen et al, 2022b;Kang et al, 2022b) and so on.…”

“…For the malignant melanoma treatment, targeted delivery of triptolide was applied with cyclopeptide and αvβ3 integrin-specific exosomes ( Gu et al, 2022 ). Accumulating evidences revealed that triptolide has a strong antitumor effect in a broad range of cancers, including non-small cell lung cancer ( Zhou et al, 2022c ), colorectal cancer ( Liskova et al, 2022 ; Song et al, 2022 ), hepatocellular carcinoma ( Li et al, 2022b ), acute myeloid leukemia ( Chen et al, 2022b ; Kang et al, 2022b ) and so on.…”