Traditional Medicinal Plants as a Source of Inspiration for Osteosarcoma Therapy

Kazantseva, Liliya; Becerra, José; Santos-Ruíz, Leonor

doi:10.3390/molecules27155008

Cited by 8 publications

(4 citation statements)

References 125 publications

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“…Osteosarcoma is a common type of cancer in orthopaedic clinics, and despite ongoing extensive research, no significant therapeutic improvements have been achieved in the last few decades [4]. Earlier findings have suggested that osteosarcoma is a highly variable cancer, both in its clinical presentation and on a cellular and molecular level [22]. Paradoxically, only four drugs, cisplatin, DOX, isocyclophosphamide, and methotrexate, are currently used to treat this cancer, and chemotherapy-induced toxicity remains an unresolved problem in osteosarcoma and other cancers [23,24].…”

Section: Discussionmentioning

confidence: 99%

Piperine improves the sensitivity of osteosarcoma cells to doxorubicin by inducing apoptosis and inhibiting the PI3K/AKT/GSK-3β pathway

Liu

et al. 2023

J Orthop Surg Res

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Background Osteosarcoma is a primary bone malignancy associated with the highest incidence rate. Chemotherapy for osteosarcoma has not substantially changed, and survival of patients with metastatic tumours has reached a plateau. Doxorubicin (DOX) is a broad-spectrum anti-osteosarcoma drug; however, its application is limited due to its high cardiotoxicity. Piperine (PIP) has been verified to drive certain cancer cell death and increases chemosensitivity of DOX. However, the effects of PIP in promoting the chemosensitivity of osteosarcoma to DOX have not been studied. Methods We examined the combined effect of PIP and DOX on U2OS and 143B osteosarcoma cells. CCK-8 assays, scratch assays, flow cytometry analysis, and western blotting were performed. Furthermore, the effect of PIP combined with DOX on osteosarcoma tumours was observed in vivo using nude mice. Results PIP can increase the chemosensitivity of U2OS and 143B cells to DOX. Both in vitro and in vivo results showed the dramatic inhibition of cell proliferation and tumour growth by the combined therapy group compared to monotherapy groups. Apoptosis analysis revealed that PIP augments DOX-induced cell apoptosis by upregulating BAX and P53 expression, as well as reducing Bcl-2 expression. Furthermore, PIP also attenuated the initiation of the PI3K/AKT/GSK-3β signaling pathway in osteosarcoma cells by altering the expression levels of P-AKT, P-PI3K and P-GSK3β. Conclusions This study revealed for the first time that PIP can potentiate the sensitivity and cytotoxicity of DOX during osteosarcoma therapy in vitro and in vivo, which probably achieved by inhibiting the PI3K/AKT/GSK-3β signalling pathway.

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Section: Discussionmentioning

confidence: 99%

Piperine improves the sensitivity of osteosarcoma cells to doxorubicin by inducing apoptosis and inhibiting the PI3K/AKT/GSK-3β pathway

Liu

et al. 2023

J Orthop Surg Res

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“…In addition, a wide variety of natural products that stimulate autophagy by interfering with the PI3K/AKT/mTOR pathway in OS cells are described in Table 2 [ 106 ].…”

Section: Modulation Of Autophagy In Os Therapeuticsmentioning

confidence: 99%

Autophagy Modulation as a Potential Therapeutic Strategy in Osteosarcoma: Current Insights and Future Perspectives

Almansa-Gómez,

Prieto-Ruiz,

Cansado

et al. 2023

IJMS

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Autophagy, the process that enables the recycling and degradation of cellular components, is essential for homeostasis, which occurs in response to various types of stress. Autophagy plays an important role in the genesis and evolution of osteosarcoma (OS). The conventional treatment of OS has limitations and is not always effective at controlling the disease. Therefore, numerous researchers have analyzed how controlling autophagy could be used as a treatment or strategy to reverse resistance to therapy in OS. They highlight how the inhibition of autophagy improves the efficacy of chemotherapeutic treatments and how the promotion of autophagy could prove positive in OS therapy. The modulation of autophagy can also be directed against OS stem cells, improving treatment efficacy and preventing cancer recurrence. Despite promising findings, future studies are needed to elucidate the molecular mechanisms of autophagy and its relationship to OS, as well as the mechanisms underlying the functioning of autophagic modulators. Careful evaluation is required as autophagy modulation may have adverse effects on normal cells, and the optimization of autophagic modulators for use as drugs in OS is imperative.

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“…Over half of anticancer drugs contain natural products with phytochemical components that offer antibacterial, anticancer, and neuroprotective effects (Choudhari et al, 2019). When focused speci cally on osteosarcoma, studies documenting the anti-cancer capabilities of plant-derived metabolites reveal a range of processes and pathways involved in creating these effects (Kazantseva et al, 2022). These phytochemicals act on several apoptotic pathways and augment the therapeutic advantages of conventional medications, they are chosen in combination therapy (Rodriguez et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Unraveling the therapeutic potential of Rutin against osteosarcoma cells: Targeting TNF-α and VEGF signaling pathways

Gnanamathy,

Sheela,

Jeevitha

et al. 2024

Preprint

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Background Rutin is a flavonoid that is widely distributed in plants and has been identified as having medicinal qualities as well as potential benefits for treating a range of ailments. In this work, we examined rutin's anticancer effects, specifically with regard to osteosarcoma, a type of bone cancer. Methods and results We evaluated the cytotoxic activity of rutin using MTT and LDH tests on the MG-63 osteosarcoma cell line, and the results showed a notable cytotoxic effect. Following rutin treatment, morphological alterations, such as membrane blebbing and cell shrinkage, were noted, which are typical of anticancer medications. Additionally, an in vitro assessment employing the wound healing assay revealed rutin's anti-migratory action on MG-63 cells. The results of the RT-PCR gene expression research pointed to possible pathways of rutin-induced apoptosis, including downregulation of the anti-apoptotic gene BCL-2 and elevation of pro-apoptotic genes including p53, Bax, and caspase-3. Additionally, the migration-causing genes VEGF and EGF were downregulated by rutin. Moreover, the relationship between rutin and proteins linked to osteosarcoma, like VEGF and TNF-α, was evaluated using in silico models. Conclusion The findings demonstrated effective binding at various binding sites, pointing to rutin's possible therapeutic use in the treatment of osteosarcoma. Although this work uses the MG-63 cell line to provide light on the anticancer activity of rutin against osteosarcoma, more preclinical research is necessary to establish the best dosages and assess safety profiles for the possible development of medications for the treatment of osteosarcoma.

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Traditional Medicinal Plants as a Source of Inspiration for Osteosarcoma Therapy

Cited by 8 publications

References 125 publications

Piperine improves the sensitivity of osteosarcoma cells to doxorubicin by inducing apoptosis and inhibiting the PI3K/AKT/GSK-3β pathway

Piperine improves the sensitivity of osteosarcoma cells to doxorubicin by inducing apoptosis and inhibiting the PI3K/AKT/GSK-3β pathway

Autophagy Modulation as a Potential Therapeutic Strategy in Osteosarcoma: Current Insights and Future Perspectives

Unraveling the therapeutic potential of Rutin against osteosarcoma cells: Targeting TNF-α and VEGF signaling pathways

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