Honokiol targets mitochondria to halt cancer progression and metastasis

Abstract

Cancer continues to be the leading cause of death worldwide. Plants have a long history of use in the treatment of cancer. Honokiol (HNK) is an important bioactive compound found in the bark of Magnolia tree, and has been shown to inhibit cancer growth and metastasis in many cell types in vitro and in animal models. Resistance to chemotherapy and radiotherapy is the major obstacle for cure of cancer. Combination of HNK with many traditional chemotherapeutic drugs as well as radiation sensitizes cancer cells to apoptotic death, suggesting that HNK not only directly inhibits primary cancers and metastasis, but also has potential to overcome drug resistance. Ultimately, this may mean that HNK could be combined with traditional chemotherapies administered at lower doses to significantly reduce toxicity, meanwhile enhance efficacy. As a natural compound, HNK is composed of polyphenols and has been described in many studies targeting multiple key cell signaling molecules. Mitochondria are the main hub for cellular energy production and play an important role in cell survival, and are the key target identified for HNK to mediate cancer cell death, survival, and metastasis. In this review, we have summarized different aspects of HNK's anti-cancer effects from recent accumulated literature, as well as the underlying molecular mechanisms. This review is primarily focused on the effects of HNK on epidermal growth factor receptor (EGFR) and signal transduction and activator of transcription 3 (STAT3) signaling, as well as the broader regulation of mitochondrial function and cancer cell metabolism.

Mitochondrial pyruvate carrier function determines cell stemness and metabolic reprogramming in cancer cells

“…Main energy source from TCA cycle occurs in the mitochondria and dysfunctional mitochondrion cause diabetes, obesity and carcinogenesis [19–21]. Knowing that mitochondria is essential to metabolism, we show herein that pyruvate transport blocking via deletion of the MPC1 gene has impact on the metabolism and biological behaviors in prostate cancer cells in vitro .…”

Honokiol Induces Apoptosis, G1 Arrest, and Autophagy in KRAS Mutant Lung Cancer Cells

“…Honokiol has generated an extensive interest in cancer research due to its multi-functional effects such as inducing anti-tumor growth, anti-migration, anti-angiogenesis and anti-multiple drug resistance (Kumar et al, 2013; Pan et al, 2016). As a novel agent for cancer therapy, honokiol, targets multiple signaling pathways, including nuclear factor kappa B (NF-κB) (Ahn et al, 2006), signal transducers and activator of transcription 3 (STAT3), epidermal growth factor receptor (EGFR) (Leeman-Neill et al, 2010; Song et al, 2016) and mammalian target of rapamycin (m-TOR) (Lin et al, 2016), all of which have great relevance during cancer initiation and progression.…”

Honokiol Alleviates Hypertrophic Scar by Targeting Transforming Growth Factor-β/Smad2/3 Signaling Pathway

“…Modern pharmacological researches have suggested that HKL has anti-inflammatory, anti-bacterial, anti-oxidant, anti-tumor, anti-calmodulin, neuroprotective, and other effects (Fried and Arbiser, 2009; Shen et al, 2010; Lee et al, 2011; Woodbury et al, 2013; Pan et al, 2016). A recent study had reported that HKL could reverse cardiac hypertrophy by inhibiting cardiac fibroblasts proliferation and differentiation to myofibroblasts (Pillai et al, 2015).…”