Chitooligosaccharides inhibit tumor progression and induce autophagy through the activation of the p53/mTOR pathway

Zhen Pan1, Dong-Dong Cheng1, Xiao-Juan Wei1

  • 1Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.

Carbohydrate Polymers
|February 17, 2021
PubMed

Insights

Chitooligosaccharide (COS) demonstrates significant anti-tumor effects against osteosarcoma cells by inhibiting growth and metastasis. This study suggests COS as a promising therapeutic candidate for osteosarcoma treatment.

Area of Science:

  • Oncology
  • Biochemistry
  • Biomaterials

Background:

  • Osteosarcoma is the most common primary bone sarcoma.
  • Chitooligosaccharide (COS) is an emerging drug carrier for cancer therapy.
  • The therapeutic potential of COS in osteosarcoma remains unexplored.

Purpose of the Study:

  • To investigate the anti-tumor effects of Chitooligosaccharide (COS) on osteosarcoma.
  • To elucidate the underlying mechanisms of COS action in osteosarcoma.
  • To evaluate COS as a potential therapeutic candidate for osteosarcoma.

Main Methods:

  • Enzymatic hydrolysis was used to obtain low-degree-polymerized COS (DP = 2-6).
  • In vitro assays assessed COS effects on osteosarcoma cell growth, metastasis, apoptosis, and autophagy.
  • An in vivo osteosarcoma xenograft model evaluated tumor growth and metastasis inhibition.
  • COS's influence on cisplatin chemotherapy sensitivity was examined.

Main Results:

  • COS exhibited significant anti-tumor activity against osteosarcoma cells in vitro.
  • COS inhibited cell growth and metastasis, and induced apoptosis and autophagy via the p53/mTOR pathway.
  • COS administration suppressed tumor growth and metastasis in vivo.
  • COS enhanced the efficacy of cisplatin chemotherapy against osteosarcoma.

Conclusions:

  • COS possesses notable anti-tumor properties against osteosarcoma.
  • COS modulates key cellular pathways involved in cancer progression.
  • COS represents a promising novel therapeutic agent for osteosarcoma treatment.

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.1K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
4.7K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.9K
Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
2.3K